On July 4, 2023 Isofol Medical AB (publ) reported the conclusions from the company’s in-depth analysis of data from the Phase III study AGENT (Press release, Isofol Medical, JUL 4, 2023, View Source [SID1234633040]). The results from the analysis support the hypothesis that a different dose and administration regimen has the potential to improve the efficacy of the company’s drug candidate arfolitixorin. Isofol has therefore decided to continue the development of arfolitixorin and is intensifying preparations for a possible start of a minor clinical study.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In preclinical and clinical studies, Isofol’s drug candidate arfolitixorin has shown the potential to improve the efficacy of the cancer drug 5-FU, which is part of the current standard treatment for colorectal cancer. However, the recent AGENT study did not show a statistically significant difference in efficacy between arfolitixorin and the standard treatment given in the control arm. Isofol therefore initiated a stepwise process in March 2023 to enable cost-effective and risk-minimizing continued development of the drug candidate arfolitixorin.

The process consists of three steps and Isofol has now completed the first step where the company has conducted an in-depth analysis of the available clinical data from the AGENT study. The aim has been to identify possible reasons why arfolitixorin in the AGENT study did not show any statistically significant difference in efficacy compared to the current standard of care. As part of the evaluation, the company, together with external experts, has also conducted PK (pharmacokinetic) modeling that calculate how drugs are absorbed, distributed and eliminated from the body.

The main conclusions of the evaluation in step 1 are:
The chosen dose and the administration regime of two bolus doses likely resulted in that the concentration of arfolitixorin in the patients’ blood was too low to deliver a sufficiently high amount of active substance into the tumor.
The consequence of the low dose, in comparison with the control group with standard treatment, was not justified because the control group was treated with a higher dose.
PK modeling and review of available safety data show that it is likely possible to administer arfolitixorin at a higher dose than that evaluated in the AGENT study and that a different dose and administration regimen could probably have improved the drug candidate’s efficacy.
Based on these conclusions, Isofol has decided to continue the development of arfolitixorin according to the previously communicated three-step process. Step two of the process has already been initiated with the Norwegian biotech company Oncosyne AS, which conducts preclinical tests in microtumors to document the effect of different doses. Results from these tests are expected after the summer.

In parallel, Isofol now intends to intensify the preparations to start a minor clinical study as soon as possible, in accordance with the third and final step in the company’s previously communicated strategy. However, a decision to start such a study will only be made when the results from step two are carefully analyzed.

Isofol continues to protect its financial position and carefully evaluates the results of each step of the strategic plan before allocating additional resources to the project. The company estimates that the planned activities will continue to be financed from existing funds.

On July 4, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, ireported that it will be commencing a pivotal Phase III trial of its 64Cu SAR-bisPSMA diagnostic in prostate cancer (PC) following a successful end of phase meeting with the US Food and Drug Administration (FDA) (Press release, Clarity Pharmaceuticals, JUL 4, 2023, View Source [SID1234633029]). The trial will be named CLARIFY (Positron Emission Tomography using 64Cu SAR-bisPSMA in participants with high-risk PC prior to radical prostatectomy: A prospective, single-arm, multi-centre, blinded-review, Phase III diagnostic performance study) and is expected to begin patient recruitment in late 2023.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The FDA is supportive of a prospective, non-randomised, single-arm, open-label, multi-center, Phase III diagnostic clinical trial of 64Cu SAR-bisPSMA PET in 383 participants with untreated, histopathology-confirmed PC, with high-risk features, who are proceeding to radical prostatectomy with pelvic lymph node dissection. As a pivotal trial, the final study results are intended to provide sufficient evidence to support an application to the FDA for approval of 64Cu SAR-bisPSMA as a new diagnostic imaging agent in PC.

The aim of the Phase III trial is to assess the diagnostic performance of 64Cu SAR-bisPSMA PET to detect PC within the pelvic lymph nodes. Evaluation will be across 2 imaging timepoints, Day 1 (day of administration) and Day 2 (approximately 24 hours post administration).

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are very excited to progress our Phase III trial and are appreciative of the time and valuable guidance the FDA has provided in relation to our 64Cu SAR-bisPSMA program during the end of phase meeting. The initiation of the CLARIFY trial is supported by compelling preclinical and clinical trial data. We would like to thank everyone who contributed to this exciting milestone, from our scientific collaborators at the University of Melbourne, who helped us overcome the low uptake and washout of first generation PSMA agents by assisting us in making an optimised PSMA agent for imaging and therapy, to the patients who participate in our clinical trials and to our incredible team and collaborators who work tirelessly towards our mutual goal of improving treatment outcomes for patients with PC. With this product, in both our diagnostic and therapy trials, we are now getting very close to achieving this goal.

"The positive results from our completed PROPELLER1 trial showed that 64Cu SAR-bisPSMA is safe, and its uptake in PSMA-expressing cancer lesions was significantly higher compared to the approved standard-of-care PSMA imaging agent for PC in Australia and the US. This may enable diagnosis of additional and smaller lesions, especially when coupled with the opportunity for delayed imaging, a characteristic not available to the first generation of PSMA imaging agents that exhibit high specificity but low sensitivity in diagnosing metastases outside of the prostate. Furthermore, we believe that the additional shelf-life of up to 48 hours could not only allow clinics greater flexibility in scheduling of the scans, but also improve patients’ access to care in clinics and geographic areas where the short half-life of current PSMA PET tracers restricts the use of radiopharmaceuticals. We look forward to opening our Phase III trial later this year to confirm and build on the positive data we have seen on the 64Cu SAR-bisPSMA product to date. Our hope is that better diagnostic tools will help clinicians determine the best course of treatment for their patients, informing a potential life-changing decision between the surgical removal of the prostate and other treatment options that may support a better quality of life post-treatment. We are excited about further exploring these clinical benefits as well as the logistical and manufacturing advantages of our Targeted Copper Theranostics (TCTs) platform and bringing this next generation PSMA diagnostic to PC patients around the world."

About SAR-bisPSMA
SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA binding motifs to Clarity’s proprietary sarcophagene (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a TCT that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu SAR-bisPSMA and 67Cu SAR-bisPSMA are investigational products and not yet approved by health authorities.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide2. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of PC in the US and around 34,700 deaths from the disease

On July 3, 2023 CANbridge Pharmaceuticals, Inc. (1228.HK), a global biopharmaceutical company, with a foundation in China, committed to the research, development and commercialization of transformative therapies to treat rare diseases and oncology, reported that, based on the interim analysis recommendation of the independent data monitoring committee, it plans to continue the ongoing Phase 2 study of CAN008 in patients with newly diagnosed glioblastoma multiforme (GBM) in China to completion (Press release, CANbridge Life Sciences, JUL 3, 2023, View Source [SID1234633035]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased that the independent data monitoring committee made the recommendation to continue the CAN008 Phase 2 glioblastoma multiforme trial in China, based on their analysis of the interim data," said James Xue, Ph.D., founder, chairman and CEO of CANbridge Pharmaceuticals Inc. "Glioblastoma is an intractable cancer with poor patient outcomes under standard-of-care. We look forward to continuing to develop CAN008 as a potentially new treatment for patients in China."

About the CAN008 Phase 2 Trial in glioblastoma multiforme (GBM)

The Phase 2 double-blinded study enrolled 119 subjects who were randomized 2:1 to receive intravenous CAN008 400 mg or placebo, in addition to standard-of-care chemoradiotherapy. All subjects underwent surgical excision of the GBM tumor prior to treatment. During the course of the study, they receive a 6-week course of triple therapy(temozolomide, radiotherapy and CAN008 or placebo), followed by a 1-month rest, then a 12-month course of dual therapy (temozolomide and CAN008 or placebo), and then monotherapy (CAN008 or placebo) until progression of disease, intolerability to treatment, death, or withdrawal. The primary endpoint is progression-free survival (PFS), and the secondary endpoint is overall survival (OS).

About CAN008

CAN008 (asunercept) is a CD95-Fc fusion protein that binds to the CD95 ligand and blocks the interaction between the ligand and the endogenous CD95 receptor. CAN008 has a unique dual mechanism of action, inhibiting both the invasive growth and migration of tumor cells, as well as T-cell apoptosis, which enhances immune recognition of the cancer. Earlier asunercept glioblastoma multiforme (GBM) clinical trial data showed favorable safety and tolerability, prolonged survival and improved quality-of-life.

Asunercept has been granted US FDA Orphan Drug Designation and Orphan Medicinal Product Designation by the European Medicines Agency (EMA) for GBM. It has also been accepted into the EMA’s PRIME (Priority Medicines) program, which provides support to medicines that could address unmet medical needs. In China, CAN008 has been classified as a Class 1 New Drug by the National Medical Products Administration. CANbridge holds the rights to develop and commercialize CAN008 for any indication in Greater China and is currently conducting a CAN008 Phase 2 trial in GBM in China.

On July 3, 2023 Lunit (KRX:328130.KQ), a global provider of AI-powered cancer diagnostics solutions, reported the publication of a study exploring the impact of medical AI solutions’ accuracy on radiologists’ diagnostic determination (Press release, Lunit, JUL 3, 2023, View Source;published-in-radiology-301868701.html [SID1234633033]). The study, conducted by Seoul National University Hospital from December 2015 to February 2021, was recently published in ‘Radiology,’ a renowned peer-reviewed journal in medical imaging.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study involved a cohort of 30 doctors, including 20 board-certified radiologists with 5 to 18 years of expertise and 10 radiology residents with 2 to 3 years of training. A total of 120 retrospectively collected chest radiographs were assessed, with 60 obtained from patients with lung cancer and the remaining 60 showing no abnormalities.

During the first session, the 30 readers were divided into two groups and analyzed 120 chest X-rays each without the assistance of AI. In the subsequent session, each group reinterpreted the images with the aid of either a high-accuracy or low-accuracy AI model.

The high-accuracy AI model utilized in the study was Lunit INSIGHT CXR, Lunit’s commercially available AI solution for chest X-ray analysis. In contrast, the low-accuracy model was trained using only 10% of the data available to Lunit INSIGHT CXR. The AUROC (area under the receiver operating characteristic curve), a commonly used metric for diagnostic accuracy, of Lunit INSIGHT CXR was 0.88, while the low-accuracy AI model only reached 0.77.

The study revealed that using the higher-accuracy AI model, Lunit INSIGHT CXR, significantly improved radiologists’ performance. The AUROC was remarkably advanced from 0.77 to 0.82 when assisted by the high-accuracy AI model.

Conversely, the radiologists from the other group did not experience any performance improvement when utilizing the low-accuracy AI model, as the AUROC remained at 0.75. Moreover, the group that employed the high-accuracy AI model demonstrated a higher susceptibility to AI suggestions. The radiologists accepted 67% of AI recommendations that contradicted the initial reading results, compared to 59% acceptance of the group that utilized the low-accuracy AI model.

Moreover, the study findings highlighted that factors such as radiologists’ individual expertise, experience with AI, or attitudes toward AI had negligible impact on their reading performance in the second session. Instead, the accuracy of the AI model and the radiologists’ initial diagnostic accuracy emerged as the primary determinant shaping the final diagnostic determination.

These findings underscore the significance of the AI model’s performance when radiologists use AI as a second reader. Furthermore, the study demonstrates how such AI assistance can increase radiologists’ susceptibility to AI suggestions, ultimately contributing to more accurate diagnoses.

"The study backs that irrespective of radiologists’ individual characteristics, the utilization of high-performance AI significantly enhances diagnostic accuracy and fosters a greater acceptance of AI within medical practices," said Brandon Suh, CEO of Lunit. "At Lunit, we are committed to developing AI-powered solutions that not only improve patient outcomes but also augment the expertise of healthcare professionals. This publication is a testament to our dedication to advancing the field of cancer diagnostics through cutting-edge technology."

Radiology, owned and published by the Radiological Society of North America (RSNA), is a prestigious publication with a distinguished Impact Factor of 29.146, making it the number one ranked journal in the field of medical imaging.

On July 4, 2023 4SC AG (4SC, FSE Prime Standard: VSC) reported that the results from the RESMAIN Study evaluating resminostat (Kinselby) in maintenance treatment of patients with advanced cutaneous T-cell lymphoma (CTCL) will be presented by Professor Dr. Rudolf Stadler at the EORTC Cutaneous Lymphoma Tumour Group Annual Meeting 2023 on Saturday, 23rd September 2023 at 9:10h CEST at The Leiden University Medical Center in the Netherlands (Press release, 4SC, JUL 3, 2023, View Source [SID1234633032]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On 23 May 2023 4SC AG informed the market that resminostat (Kinselby) had met the primary endpoint in the RESMAIN study and demonstrated a statistically significant improvement in progression free survival in CTCL patients by ninety seven point six percent (97.6%) with a risk reduction of thirty eight percent (38%) compared to placebo. The study confirmed the already well known safety profile of resminostat (Kinselby) in CTCL.

RESMAIN is a pivotal study, conducted as a multi-center, double blind, randomized, placebo-controlled study, evaluating resminostat for maintenance treatment of patients with advanced-stage cutaneous T-cell lymphoma (CTCL) who have achieved disease control with prior systemic therapy, at 50 clinical centers in 11 European countries and 5 centers in Japan.

If approved by regulatory authorities, resminostat (Kinselby) would be the first histone deacetylase inhibitor approved in Europe for CTCL and the first and only drug approved for maintenance therapy in this disease, making it the Company’s most valuable asset. The positive outcome to RESMAIN creates an opportunity to either sell, license or partner 4SC’s resminostat program for commercialization worldwide (excluding Japan), where Yakult Honsha Co. Ltd, was granted an exclusive license for the development and marketing of resminostat in Japan in 2011.

Dr. Susanne Danhauser-Riedl, Chief Medical Officer of 4SC: "The RESMAIN study is the first randomised controlled trial that has proven the benefit of maintenance treatment in advanced CTCL, and we are very pleased to have successfully demonstrated the positive impact of using resminostat for patients enrolled in this study. We thank the investigators and their staff and in particular the patients that participated in the RESMAIN trial and made this success happen".